The carotenoids are important natural products which are involved in the photosynthetic process of plants. Carotenoids are used as nutritional supplements for animals and humans, as well as in food colorants and cosmetics. Although carotenoids are important for health, animals and humans cannot produce them, and these compounds must thus be obtained through diet from fruits and vegetables.
Several properties of the carotenoids make them important for the health of both animals and humans. For example, these compounds are antioxidants with important quenching effects on free radicals. They protect living tissues against a variety of diseases, either directly or as immunopotentiators. Additionally, carotenoids are involved in gap-junction communication among living cells. Recent epidemiological evidence has suggested an inverse relationship between the consumption of fruits and vegetables with high carotenoid content and the incidence of several types of cancers. Specifically, xcex2-carotene, lutein and lycopene have been shown to exhibit a cancer-prevention effect (M. M. Mathews-Roth, Current Chemotherapy and Infectious Diseases (J. D. Nelson and C. Grassi, Eds, Am. Soc. Microbiol., Washington D.C.:1503-1505(1980)); B. P. Chew et al, Anticancer Research 16:3689-3694 (1996); P. H. Gann et al, Cancer Res. 59:1225-1230 (1999)).
Additionally, several carotenoids, such as lutein and zeaxanthin, have specific functions in the retina of the eye to assure healthy vision in several animal species, including humans (J. D. Landrum et al., Archives Biochem. Biophys. 385(1):28-40(2001)). Finally, some carotenoids have pro-vitamin A activity, whereas others control reproduction and fertility, upregulate the Connexin43 gene, decrease the risk of degenerative disease and prevent coronary heart disease (N. Krinsky, Pure and Appl. Chem. 66(5):1003-1010 (1994)).
From a chemical standpoint, carotenoids may be classified by their functional groups into several categories (see Key to Carotenoids, 2nd enlarged and revised edition, H. Pfander et al, Birkhxc3xa4user Verlag, Basel, 1987). These include hydrocarbon carotenoids such as xcex2-carotene and lycopene, monohydroxy carotenoids such as xcex2-cryptoxanthin, dihydroxy carotenoids such as lutein and zeaxanthin, polyhydroxy carotenoids such as xcex2,xcex2-carotene triol, epoxycarotenoids such as violaxanthin and antheraxanthin, carbonyl carotenoids such as echinenone, capsanthin, canthaxanthin and astaxanthin, and carotenoid acids such as bixin and crocetin.
Esters with a carotenoid as the alcohol-derived moiety are well known. For example, the monoesters and diesters of lutein and zeaxanthin with palmitic acid, myristic acid and stearic acid occur in nature. They are also known as the xe2x80x9cxanthophyllsxe2x80x9d of the flowers and leaves of most plants (Alam, Lipids, 3:183 (1968)). These esters are also prepared commercially, as described, for example, in U.S. Pat. No. 6,191,293 of Levy via the extraction of the flowers of the marigold plant (Tagetes erecta) with subsequent purification.
Additionally, some esters containing a carotenoid as the alcohol-derived moiety have been prepared synthetically. For example, the valerate, laurate, oleate, linoleate and caproate esters of the carotenoids zeaxanthin and isozeaxanthin have been described in U.S. Pat. No. 5,536,504 of Eugster, et al. Short chain organic acid diesters of lutein and zeaxanthin have also been described in U.S. Pat. No. 5,959,138 of Torres-Cardona, et al.
Esters containing a carotenoid as the acid-derived moiety are also well known. Whereas many occur in nature (xe2x80x9cKey to Carotenoidsxe2x80x9d), other esters of this type have been prepared by synthesis. For example, U.S. Pat. No. 2,768,198 of Marbet, et al. describes the preparation of esters of bixin and norbixin with amyl alcohol, octyl alcohol and Vitamin A.
Finally, glycerides with a carotenoid acid have been prepared by enzymatic catalysis (Partali et al, Angew. Chem Int. Ed. Engl. 35:329-330 (1996)). The reaction of xcex2-apo-8xe2x80x2-carotenoic acid with Vitamin E yields xcex1-tocopheryl-xcex2-8xe2x80x2-carotenoate as described by Larsen et al (Chem. Eur. J. 4:113-117 (1998)). Additionally, the enzymatic esterification of bixin using L-ascorbic acid, which contains two alcoholic OH groups, as the alcohol moiety has been reported by Humeau et al (Biotechnol. Lett. 22:155-168 (2000)).
In summary, although many esters containing carotenoid components are known, all of the known carotenoid esters contain a non-carotenoid component as the alcohol-derived moiety or the acid-derived moiety.
This invention is directed to esters comprising at least one alcohol-derived moiety and at least one acid-derived moiety, wherein the at least one alcohol-derived moiety comprises a hydroxy carotenoid selected from the group consisting of monohydroxy carotenoids, dihydroxy carotenoids, and polyhydroxy carotenoids, and wherein the acid-derived moiety comprises a carboxylic carotenoid selected from the group consisting of monocarboxylic carotenoids, dicarboxylic carotenoids, and polycarboxylic carotenoids. Preferred hydroxy carotenoids include lutein, zeaxanthin, cryptoxanthin, violaxanthin, carotene diol, hydroxy carotene, hydroxylycopene, alloxanthin and dehydrocryptoxanthin. Preferred carboxylic carotenoids include bixin, norbixin, xcex2-apo-8-carotenoic acid, crocetin, diapocarotenoic acid, carboxylcarotene and azafrin.